MEFENAMIC ACID
Cardiovascular Risk
Gastrointestinal Risk
|
DRUG PRESENTATION
Film-coated tablet.
COMPOSITION
Film-coated tablet: Mefenamic acid 500 mg.
DRUG LIST CLASSIFICATION
Prescription drug
ACTIONS
Mefenamic acid is non steroid antiinflammation that act by inhibiting prostaglandin synthesis process in body tissue by inhibiting cyclooxygenize enzymes therefore it has analgesic, antiinflammation and antipyretic effects.
METABOLISM
Mefenamic acid metabolism is predominantly mediated via cytochrome P450 CYP 2C9 in the liver. Patients who are known or suspected to be poor CYP2C9 metabolizers based on previous history/experience with other CYP2C9 substrates should be administered mefenamic acid with caution as they may have abnormally high plasma levels due to reduced metabolic clearance.
USAGE
Oral
INDICATIONS
Relief mild to medium pain such as headache, toothache, primary dysmenorrhea, including pain caused by trauma, muscular pain and pain after surgery.
CONTRAINDICATIONS
- Hypersensitivity to mefenamic acid or any components of this product.
- Patient experiencing bronchospasm, allergic rhinitis, and urticaria when treated with acetyl salysilic acid or other non steroidal anti-inflammatory drugs.
- Patient with active ulceration or chronic inflammation of either the upper or lower gastrointestinal tract.
- Patients with pre-existing renal disease.
- Treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery.
- Patients with severe renal and hepatic failure.
- Patients with severe heart failure.
DOSAGE AND ADMINISTRATION
Undesirable effects may be minimized by using the minimum effective dose for the shortest duration necessary to control symptoms.
Adults and children › 14 years old:
Initial dose: 500 mg, continue with 250 mg every 6 hours, as needed
UNDESIRABLE EFFECTS
Blood and lymphatic system disorders: agranulocytosis, aplastic anemia, autoimmune hemolytic anemia*, bone marrow hypoplasia, decreased hematocrit, eosinophilia, leukopenia, pancytopenia and thrombocytopenia purpura.
Immune system disorders: anaphylaxis.
Metabolism and nutrition disorders: glucose intolerance in diabetic patients, hyponatremia.
Psychiatric disorders: nervousness
Nervous system disorders: aseptic meningitis, blurred vision, convulsions, dizziness, drowsiness, headache and insomnia.
Eye disorders: eye irritation, reversible loss of color vision.
Ear and labyrinth disorders: ear pain.
Cardiac disorders: palpitation.
Vascular disorders: hypotension.
Respiratory, thoracic and mediastinal disorders: asthma, dyspnea.
Gastrointestinal disorders: the most frequently reported side effects associated with mefenamic acid involve the gastrointestinal tract. Diarrhea appears to be the most common side effect and is usually dose-related. It generally subsides on dosage reduction, and rapidly disappears on termination of therapy. Some patients may not be able to continue therapy.
The following are the most common gastrointestinal side effects: abdominal pain, diarrhea and nausea with or without vomiting.
Less frequently reported gastrointestinal / hepatobiliary side effects include: anorexia, cholestatic jaundice, colitis, constipation, enterocolitis, flatulence, gastric ulceration with and without hemorrhage, mild hepatic toxicity, hepatitis, hepatorenal syndrome, pyrosis, pancreatitis and steatorrhea.
Skin and subcutaneous tissue disorders: angioedema, edema of the larynx, erythema multiforme, facial edema, Lyell's syndrome (toxic epidermal necrolysis), perspiration, pruritus, rash, Stevens-Johnson syndrome and urticaria.
Renal and urinary disorders: dysuria, hematuria, renal failure including papillary necrosis and tubulointerstitial nephritis.
Paediatric patients
General disorders and administration site conditions: hypothermia.
*Reports are associated with ≥ 12 months of mefenamic acid therapy and the anemia is reversible with discontinuation of therapy.
WARNINGS AND PRECAUTIONS
The use of mefenamic acid with concomitant NSAIDs including COX-2 inhibitors should be avoided.
Cardiovascular Thrombotic Events
Clinical trials of several COX-2 selective and non-selective NSAIDs of up to three years duration have shown an increase risk of serious cardiovascular (CV) thrombotic events, myocardial infarction, and stroke, which can be fatal.
All NSAIDs, both COX-2 selective and non-selective, may have a similar risk. Patients with known CV disease or risk factors for CV disease may be at greater risk. To minimize the potential risk for an adverse CV event in patients treated with an NSAID, the lowest effective dose should be used for the shortest duration possible. Physicians and patients should remain alert for the development of such events, even in the absence of previous CV symptoms. Patients should be informed about the signs and/or symptoms of serious CV events and the steps to take if they occur.
There is no consistent evidence that concurrent use of acetyl salicylic acid mitigates the increased risk of serious CV thrombotic events associated with NSAID use. The concurrent use of acetyl salicylic acid and an NSAID does increase the risk of serious GI events (see GI WARNINGS, Gastrointestinal (GI) Effect-Risk of GI Ulceration, Bleeding and perforation).
Two large, controlled, clinical trials of a COX-2 selective NSAID for the treatment of pain in the first 10-14 days following CABG surgery found an increased incidence of myocardial infarction and stroke (see section CONTRAINDICATIONS).
Hypertension
NSAIDS, including PONSTAN can lead to onset of new hypertension or worsening of pre-existing hypertension, either of which may contribute to the increased incidence of CV events. Patients taking thiazides or loop diuretics may have impaired response to these therapies when taking NSAIDs. NSAlDs, including PONSTAN, should be used with caution in patients with hypertension. Blood pressure (BP) should be monitored closely during the initiation of NSAID treatment with PONSTAN and throughout the course of therapy.
Congestive Heart failure and Edema
Fluid retention and edema have been observed in some patients taking NSAIDs, including PONSTAN. PONSTAN should be used with caution in patients with fluid retention or heart failure.
Gastrointestinal (GI) Effects- Risk of GI Ulceration, Bleeding, and Perforation
NSAIDs, including PONSTAN, can cause serious gastrointestinal events including, inflammation, bleeding, ulceration, and perforation of the stomach, small intestine or large intestine, which can be fatal. These serious adverse events can occur at any time, with or without warning symptoms, in patients treated with NSAIDs. Only one in five patients, who develop a serious upper GI adverse event on NSAID therapy, is symptomatic. Upper GI ulcers, gross bleeding, or perforation caused by NSAIDs occur in approximately 1% of patients treated for 3-6 months, and in about 2-4 % of patients treated for one year. These trends with longer duration of use, increasing the like hood of developing a serious GI event at some time during the course of therapy. However, even short-term therapy is not without risk.
NSAIDs should be prescribed with extreme caution in patients with a prior history of ulcer disease or gastrointestinal bleeding. Patients with a prior history of peptic ulcer disease and/or gastrointestinal bleeding and who use NSAIDs, have a greater than 10-fold higher risk for developing a GI bleed compared to patients with neither of these risk factors. Other factors that increase the risk for GI bleeding in patients treated with NSAIDs include concomitant use of oral corticosteroids or anticoagulants, longer duration of NSAID therapy, smoking, use of alcohol, older age, and poor general health status. Most spontaneous reports of fatal GI events are in elderly or debilitated patients and therefore, special care should be taken in treating this population.
To minimize the potential risk tor an adverse GI event, In patients treated with NSAIDs, the lowest effective dose should be used for the shortest possible duration. Patients and physicians should remain alert for signs and symptoms of GI ulceration and bleeding during NSAID therapy and promptly initiate additional evaluation and treatment if a serious GI adverse event is suspected. This should include discontinuation of the NSAID until a serious GI adverse event is ruled out. For high-risk patients, alternate therapies that do not involve NSAIDs should be considered.
Skin Reactions
Serious skin reactions, some of them fatal, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, have been reported very rarely in association with the use of NSAIDs, including mefenamic acid. Patients appear to be at highest risk for these events early in the course of therapy, the onset of the event occurring in the majority of cases within the first month of treatment. Mefenamic acid should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity.
Renal Effects
In rare cases, NSAIDs, including mefenamic acid, may cause interstitial nephritis, glomerulitis, papillary necrosis and the nephrotic syndrome. NSAIDs inhibit the synthesis of renal prostaglandin which plays a supportive role in the maintenance of renal perfusion in patients whose renal blood flow and blood volume are decreased. In these patients, administration of an NSAID may precipitate overt renal decompensation, which is typically followed by recovery to pre-treatment state upon discontinuation of NSAID therapy. Patients at greatest risk of such a reaction are those with congestive heart failure, liver cirrhosis, nephritic syndrome, overt renal disease and the elderly. Such patients should be carefully monitored while receiving NSAID therapy.
Discontinuation of non steroidal anti-inflammatory drug (NSAID) therapy is typically followed by recovery to the pre-treatment state. Since mefenamic acid metabolites are eliminated primarily by the kidneys, the drug should not be administered to patients with significantly impaired renal function.
Laboratory Tests
A false-positive reaction for urinary bile, using the diazo tablet test, may result following mefenamic acid administration. If biliuria is suspected, other diagnostic procedures, such as the Harrison spot test, should be performed.
Hematologic Effects
Mefenamic acid can inhibit platelet aggregation and may prolong prothrombin time in patients on warfarin therapy. (See section DRUG INTERACTIONS)
Hepatic Effects
Borderline elevations of one or more liver function tests may occur in some patients receiving mefenamic acid therapy. These elevations may progress, may remain essentially unchanged, or may be transient with continued therapy. A patient with symptoms and/or signs suggesting liver dysfunction, or in whom an abnormal liver test has occurred, should be evaluated for evidence of the development of a more severe hepatic reaction while on therapy with mefenamic acid. If abnormal liver tests persist or worsen, if clinical signs and symptoms consistent with liver disease develop, or if systemic manifestations occur, mefenamic acid should be discontinued.
Pregnancy and lactation
Pregnancy
Since there are no adequate and well-controlled studies in pregnant women, this drug should be used only if the potential benefits to the mother justify the possible risks to the fetus. It is not known if mefenamic acid or its metabolites cross the placenta. However, because of the effects of drugs in this class (i.e., inhibitors of prostaglandin synthesis) on the fetal cardiovascular system (e.g., premature closure of the ductus arteriosus), the use of mefenamic acid in pregnant women should be avoided. Mefenamic acid inhibits prostaglandin synthesis which may result in prolongation of pregnancy and interference with labor when administered late in the pregnancy. Women on mefenamic acid therapy should consult their physician if they decide to become pregnant.
Lactation
Trace amounts of mefenamic acid may be present in breast milk and transmitted to the nursing infant. Therefore, mefenamic acid should not be taken by nursing mothers.
EFFECT ON ABILITY TO DRIVE AND USE MACHINES
Undesirable effects such as dizziness, drowsiness, fatigue and visual disturbances are possible alter taking NSAIDS. If affected, patients should not drive or operate machinery.
DRUG INTERACTIONS
Anticoagulants: Mefenamic acid has been shown to displace warfarin from protein binding sites, and may enhance the response to oral anticoagulants. Therefore, concurrent administration of mefenamic acid with oral anticoagulant drugs requires frequent prothrombin time monitoring.
Anti-hypertensives including diuretics, angiotensin-converting enzyme (ACE) Inhibitors and angiotensin II antagonists (AIIA): NSAIDs can reduce the efficacy of diuretics and other antihypertensive drugs.
In patients with impaired renal function (e.g. dehydrated patients or elderly patients with compromised renal function), the co-administration of an ACE inhibitor or an AIIA with a cyclo-oxygenase inhibitor can increase the deterioration of the renal function, including the possibility of acute renal failure, which is usually reversible. The occurrence of these interactions should be considered in patients taking mefenamic acid with an ACE inhibitor or an AIIA.
Therefore, the concomitant administration of these drugs should be done with caution, especially in elderly patients. Patients should be adequately hydrated and the need to monitor the renal function should be assessed in the beginning of the concomitant treatment and periodically thereafter.
Corticosteroids: Increased risk of gastrointestinal ulceration or bleeding.
Cyclosporine: Because of their effect on renal prostaglandins, cyclooxygenase inhibitors such as diclofenac can increase the risk of nephrotoxicity with cyclosporine.
Hypoglycemic agents: There have been reports of changes in the effects of oral hypoglycemic agents in the presence of NSAIDs. Therefore, mefenamic acid should be administered with caution in patients receiving insulin of oral hypoglycemic agents.
Lithium: Mefenamic acid has produced an elevation of plasma lithium levels and a reduction in renal lithium clearance. Thus, when mefenamic acid and lithium are administered concurrently, patients should be observed carefully for signs of lithium toxicity.
Methotrexate: Caution is advised when methotrexate is administered concurrently with NSAIDs, including mefenamic acid, because NSAID administration may result in increased plasma levels of methotrexate.
Tacrolimus: Possible increased risk of nephrotoxicity when NSAIDs are given with tacrolimus.
OVER DOSAGE
Following accidental over dosage, the stomach should be emptied immediately by inducing emesis or by gastric lavage, followed by administration of activated charcoal. Vital functions should be monitored and supported. Hemodialysis is of little value since mefenamic acid and its metabolites are firmly bound to plasma proteins.
Seizures, acute renal failure, coma, confusional state, vertigo, and hallucination have been reported with mefenamic acid overdoses. Overdose has led to fatalities.
STORAGE
store below 30°C, protect from light
SUPPLY
Ponstan FCT 500 mg, box of 10 blister @ 10 tablets; Reg.No: DKL8519807117Al
Ponstan FCT 500 mg, box of 1 blister @ 10 tablet; Reg. No: DKL8519807117A1
HARUS DENGAN RESEP DOKTER
Manufactured by :
PT. Pfizer Indonesia
PO Box 2706, Jakarta, Indonesia
PT. Pfizer Indonesia
LPG Date: October 31,2011
Supersedes: June 17, 2009
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